Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9052 |
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| author | Indrek Teino Antti Matvere Martin Pook Inge Varik Laura Pajusaar Keyt Uudeküll Helen Vaher Annika Trei Arnold Kristjuhan Tõnis Org Toivo Maimets |
| author_facet | Indrek Teino Antti Matvere Martin Pook Inge Varik Laura Pajusaar Keyt Uudeküll Helen Vaher Annika Trei Arnold Kristjuhan Tõnis Org Toivo Maimets |
| author_sort | Indrek Teino |
| collection | DOAJ |
| description | Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types. |
| first_indexed | 2024-03-10T14:29:19Z |
| format | Article |
| id | doaj.art-9d7b952ae6dd436f878df333255284a8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:29:19Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d7b952ae6dd436f878df333255284a82023-11-20T22:43:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123905210.3390/ijms21239052Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early DifferentiationIndrek Teino0Antti Matvere1Martin Pook2Inge Varik3Laura Pajusaar4Keyt Uudeküll5Helen Vaher6Annika Trei7Arnold Kristjuhan8Tõnis Org9Toivo Maimets10Chair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaChair of Cell Biology, Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, EstoniaAryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation. The purpose of this study was to investigate the temporal pattern of AHR expression during directed differentiation of human embryonic stem cells (hESC) into neural progenitor, early mesoderm and definitive endoderm cells. Additionally, we investigated the effect of the AHR agonist 2,3,7,8-tetrachlorodibenzo-<i>p</i>-dioxin (TCDD) on the gene expression profile in hESCs and differentiated cells by RNA-seq, accompanied by identification of AHR binding sites by ChIP-seq and epigenetic landscape analysis by ATAC-seq. We showed that AHR is differentially regulated in distinct lineages. We provided evidence that TCDD alters gene expression patterns in hESCs and during early differentiation. Additionally, we identified novel potential AHR target genes, which expand our understanding on the role of this protein in different cell types.https://www.mdpi.com/1422-0067/21/23/9052aryl hydrocarbon receptorhuman embryonic stem cellsneural progenitorsearly mesodermdefinitive endodermTCDD |
| spellingShingle | Indrek Teino Antti Matvere Martin Pook Inge Varik Laura Pajusaar Keyt Uudeküll Helen Vaher Annika Trei Arnold Kristjuhan Tõnis Org Toivo Maimets Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation International Journal of Molecular Sciences aryl hydrocarbon receptor human embryonic stem cells neural progenitors early mesoderm definitive endoderm TCDD |
| title | Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation |
| title_full | Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation |
| title_fullStr | Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation |
| title_full_unstemmed | Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation |
| title_short | Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation |
| title_sort | impact of ahr ligand tcdd on human embryonic stem cells and early differentiation |
| topic | aryl hydrocarbon receptor human embryonic stem cells neural progenitors early mesoderm definitive endoderm TCDD |
| url | https://www.mdpi.com/1422-0067/21/23/9052 |
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